At the end of the trials, the serum concentrations of total testosterone, free testosterone, dihydrotestosterone, estradiol, and sex hormone–binding globulin were measured in serum samples frozen at −80°C (see the Supplementary Appendix , available at NEJM.org). Steroid assays were performed at the Brigham Research Assay Core Laboratory (Boston) by liquid chromatography with tandem mass spectroscopy, and free testosterone was measured by equilibrium dialysis. All samples from each participant were measured in the same assay run.
Serum prostate-specific antigen (PSA) was measured and a digital rectal examination was performed at months 3 and 12, and PSA was measured at month 18. Detection of a prostate nodule or a confirmed increase in the PSA level by at least 1.0 ng per milliliter above baseline led to referral to the site urologist for consideration of prostate biopsy. The IPSS was determined at months 3 and 12. At every visit, adverse events were recorded and a cardiovascular-event questionnaire (see the protocol) was administered. Cardiovascular events were adjudicated by two cardiologists and two neurologists (see theSupplementary Appendix ).
Serum prostate-specific antigen (PSA) was measured and a digital rectal examination was performed at months 3 and 12, and PSA was measured at month 18. Detection of a prostate nodule or a confirmed increase in the PSA level by at least 1.0 ng per milliliter above baseline led to referral to the site urologist for consideration of prostate biopsy. The IPSS was determined at months 3 and 12. At every visit, adverse events were recorded and a cardiovascular-event questionnaire (see the protocol) was administered. Cardiovascular events were adjudicated by two cardiologists and two neurologists (see the
